Voltage-gated sodium channels are critical to the initiation and propagation of nerve action potentials and some sodium channel (NaCh) isoforms are preferentially expressed in primary afferent nociceptors. Experimental animal and a few human studies have shown changes in the distribution and expression of certain isoforms within primary afferent neurons associated with peripheral inflammation and following nerve injury. These alterations implicate dynamic NaCh expression as a basic underlying mechanism contributing to inflammatory and neuropathic pain. The tooth pulp is a rich source of pain fibers and represents a valuable model system to study pain mechanisms. Normal wisdom teeth and diseased teeth with a diagnosis of irreversible pulpitis and known pain levels are commonly extracted, providing an ample supply of tissues for analysis. The responses to sensory stimuli can be evaluated prior to extraction, thus allowing a possible correlation of NaCh expression with receptor expression for various stimuli. The overall objective of this study is to correlate changes in NaCh expression with changes in hot and cold thermoreceptors to pain levels and clinical responses to hot and cold stimuli in normal and diseased human extracted teeth. NaCh and thermoreceptor expressions will be quantified in normal and in modaUty-specific pain groups of diseased teeth. We hypothesize that in painful teeth the expression of NaCh isoforms dynamically changes, and further that these changes will correlate temporally and spatially with the expression of appropriate thermoreceptors in hot or cold sensitive painful teeth when compared to normal teeth. In a more general sense, the extracted tooth represents a powerful model system to evaluate in a quantitative fashion a possible correlation between known pain states and the alterations in diseased human tissues at the molecular level. Findings from this study will further our knowledge regarding both basic pain mechanisms and the increased occurrence of local anesthesia failures in diseased teeth that can be a major deterrent for utilization of dental care.